DEXTROMETHORPHAN–BUPROPION

brands

Class

• Antidepressant

DEXTROMETHORPHAN–BUPROPION commonly prescribed for

(Bold for FDA approved)

How DEXTROMETHORPHAN–BUPROPION works

• Dextromethorphan is a nonselective, noncompetitive NMDA receptor antagonist and a sigma 1 receptor agonist</br>

• NMDA antagonism leads to downstream glutamate release and consequent stimulation of other glutamate receptors, including AMPA receptors</br>

• Theoretically, dextromethorphan may have antidepressant effects because activation of AMPA receptors leads to activation of signal transduction cascades, including mTORC1, and an increase in growth factors such as BDNF, that cause the expression of synaptic proteins and an increase in the density of dendritic spines</br>

• Dextromethorphan also has affinity for the serotonin transporter and may therefore modulate serotonin levels</br>

• Bupropion increases availability of dextromethorphan by inhibiting its metabolism via CYP2D6</br>

• Bupropion also blocks reuptake of both norepinephrine and dopamine, presumably increasing noradrenergic and dopaminergic neurotransmission

How long until DEXTROMETHORPHAN–BUPROPION works

• Antidepressant effects can occur as early as 1 week but take up to 6 weeks

Notable Side Effects

• Dizziness, headache, somnolence

• Diarrhea, dry mouth, hyperhidrosis

• Sexual dysfunction

Life Threatening Side Effects

• Increased blood pressure

• Rare seizures (risk increases with dose; risk increases for patients with predisposing factors)

• Rare induction of mania

• Rare activation of suicidal ideation and behavior (suicidality) (short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo beyond age 24)

weight gain

unusual

sedation

not usual

What to do about DEXTROMETHORPHAN–BUPROPION side effects

• Wait

• In a few weeks, switch to another agent or add other drugs

usual dosage range

• 90 mg/210 mg dextromethorphan/ bupropion

Dosage Forms

• Extended-release tablet 45 mg/105 mg dextromethorphan/bupropion

long term use

• Not evaluated

habit forming

• No

• Formulations of bupropion have been abused by individ

Renal Impairment

• Moderate impairment (estimated GFR 30–59 mL/minute/1.73 m2 ): 45 mg/105 mg dextromethorphan/bupropion once daily in the morning

• Severe impairment: avoid use

Hepatic Impairment

• Dose adjustment not necessary in patients with mild to moderate impairment

• Not recommended in patients with severe impairment

Cardiac Impairment

• Use with caution

• May increase blood pressure

Elderly

• Some patients may tolerate lower doses better

• Reduction in the risk of suicidality with antidepressants compared to placebo in adults age 65 and older

Children and Adolescents

• Safety and efficacy have not been established

• Use with caution, observing for activation of known or unknown bipolar disorder and/or suicidal ideation, and strongly consider informing parents or guardian of this risk so they can help observe child or adolescent patients

Pregnancy

• Controlled studies have not been conducted in pregnant women

• Epidemiological studies with bupropion do not indicate increased risk of congenital malformations overall or of cardiovascular malformations

• When dextromethorphan–bupropion was administered to pregnant mice during the period of organogenesis, the no-effectrecommended human dose (MRHD), based on mg/m2

• In animal studies of bupropion administration during pregnancy, no clear evidence of teratogenicity has been observed; however, slightly increased incidences of fetal malformations and skeletal variations were observed in rabbit studies at doses approximately equal to and greater than the MRHD, and decreased fetal weights were observed at approximately 2 times the MRHD

• Neurotoxicity findings were observed when dextromethorphan–quinidine was administered to juvenile rats on postnatal day 7, which corresponds to the third trimester of gestation through the first few months of life and may extend through the first 3 years of life in humans

• Not generally recommended for use during pregnancy

• Must weigh the risk of treatment (first trimester fetal development, third trimester newborn delivery) to the child against the risk of no treatment (recurrence of depression, maternal health, infant bonding) to the mother and child level for reproductive organ findings was approximately 3.7/3.5 times the maximum

Breast Feeding

• Bupropion is found in mother’s breast milk

• Unknown if dextromethorphan is secreted in human breast milk, but all psychotropics are assumed to be secreted in breast milk

• Recommended either to discontinue drug or formula feed

• Infants of women who choose to breast feed while on dextromethorphan–bupropion should be monitored for possible adverse effects